First name
Serena
Last name
Buontempo
Year of Study
Thesis Title
Functional dissection of Ezh2 during neuraldifferentiation
Thesis Abstract
Epigenetic control of developmental genes is a key mechanism to achieve a time-regulated expression during differentiation as demonstrated to date in several differentiation pathways. In embryonic stem cells these developmental genes are marked by histone H3 lysine 4 (H3K4me3) and histone H3 lysine 27 (H3K27me3) trimethylation. The preservation of these bivalent marks is essential for proper time-regulated expression. It has been shown however that H3K27me3, catalyzed by Ezh2 within Polycomb Repressive Complex 2 is critical for the entire process of differentiation. Thus during neural differentiation, Polycomb targets have been shown to be dynamic with new genes acquiring or losing the mark at each step of neural differentiation. However most of the efforts were done on lineage commitment while Ezh2 role in the late phases of neural differentiation is less studied.
In this work the role of the epigenetic axis focusing on Ezh2 loss in post-mitotic neurons was dissected. To this end, after ES cells derivation from Ezh2 conditional mice, a neural differentiation protocol was used to produce a homogeneous population of glutamatergic post-mitotic neurons.
The lack of Ezh2 does not impair survival and development of neurons in culture. Although genome-wide transcriptomic approach revealed that Ezh2 is needed in post-mitotic neurons to maintain proper gene expression of genes involved in glutamate transmission, in particular our analysis shows an imbalance in glutamate receptors subunits expression. Thus our data suggest that post-mitotic neuronal maturation might be epigenetically controlled through Ezh2 regulation of glutamatergic pathway.
In this work the role of the epigenetic axis focusing on Ezh2 loss in post-mitotic neurons was dissected. To this end, after ES cells derivation from Ezh2 conditional mice, a neural differentiation protocol was used to produce a homogeneous population of glutamatergic post-mitotic neurons.
The lack of Ezh2 does not impair survival and development of neurons in culture. Although genome-wide transcriptomic approach revealed that Ezh2 is needed in post-mitotic neurons to maintain proper gene expression of genes involved in glutamate transmission, in particular our analysis shows an imbalance in glutamate receptors subunits expression. Thus our data suggest that post-mitotic neuronal maturation might be epigenetically controlled through Ezh2 regulation of glutamatergic pathway.
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